8.A.201. The PacL1 Chaparone Protein (PacL1) Family Heavy metal cation-transporting P-type ATPase, CtpC; MtaA; Rv3270; FUPA32.2 (718 aas with at least 8 TMSs in a 4 + 2 + 2 TMS arrangement). However, there may be additional TMSs. It mediates resistance to zinc poisoning. Boudehen et al. 2022 showed that zinc resistance also depends on a chaperone-like protein, PacL1 (Rv3269). PacL1 contains an N-terminal TMS, a cytoplasmic region with glutamine/alanine repeats and a C-terminal metal-binding motif (MBM). PacL1 binds Zn²⁺, but the MBM is required only at high zinc concentrations. PacL1 co-localizes with CtpC, a heavy metal cation-transporting P-type ATPase, in dynamic foci in the mycobacterial plasma membrane, and the two proteins form high molecular weight complexes. Foci formation does not require flotillin or the PacL1 MBM. However, deletion of the PacL1 Glu/Ala repeats leads to loss of CtpC and sensitivity to zinc. Genes pacL1 and ctpC appear to be in the same operon, and homologous gene pairs are found in the genomes of other bacteria. PacL1 colocalizes and functions redundantly with other PacL orthologs in M. tuberculosis. Thus, PacL proteins may act as scaffolds that assemble P-ATPase-containing metal efflux platforms, mediating bacterial resistance to metal poisoning (Boudehen et al. 2022).
References:
Boudehen, Y.M., M. Faucher, X. Maréchal, R. Miras, J. Rech, Y. Rombouts, O. Sénèque, M. Wallat, P. Demange, J.Y. Bouet, O. Saurel, P. Catty, C. Gutierrez, and O. Neyrolles. (2022). Mycobacterial resistance to zinc poisoning requires assembly of P-ATPase-containing membrane metal efflux platforms. Nat Commun 13: 4731.
Padilla-Benavides, T., J.E. Long, D. Raimunda, C.M. Sassetti, and J.M. Argüello. (2013). A novel P(1B)-type Mn²⁺-transporting ATPase is required for secreted protein metallation in mycobacteria. J. Biol. Chem. 288: 11334-11347.
Examples:
TC#	Name	Organismal Type	Example
8.A.201.1.1	PacL1 (Rv3269) of 93 aas and 1 N-terminal TMS. It functions with a high affinity, slow turnover heavy metal transporting ATPase CtpC (Rv3270; TC#3.A.3.32.2), which is required for virulence. It controls the Mn²⁺ cytoplasmic quota and is involved in the uploading of Mn²⁺ into secreted metalloproteins (Padilla-Benavides et al. 2013). It shows a preference for Mn²⁺, but Zn²⁺, Co²⁺ and Cu²⁺ can act as alternative substrates although at slower turnover rates (Padilla-Benavides et al. 2013). Boudehen et al. 2022 showed that zinc resistance also depends on a chaperone-like protein, PacL1 (Rv3269). PacL1 contains an N-terminal TMS, a cytoplasmic region with glutamine/alanine repeats and a C-terminal metal-binding motif (MBM). PacL1 binds Zn²⁺, but the MBM is required only at high zinc concentrations. PacL1 co-localizes with CtpC, a heavy metal cation-transporting P-type ATPase, in dynamic foci in the mycobacterial plasma membrane, and the two proteins form high molecular weight complexes. Foci formation does not require flotillin or the PacL1 MBM. However, deletion of the PacL1 Glu/Ala repeats leads to loss of CtpC and sensitivity to zinc. Genes pacL1 and ctpC appear to be in the same operon, and homologous gene pairs are found in the genomes of other bacteria. PacL1 colocalizes and functions redundantly with other PacL orthologs in M. tuberculosis. Thus, PacL proteins may act as scaffolds that assemble P-ATPase-containing metal efflux platforms, mediating bacterial resistance to metal poisoning (Boudehen et al. 2022).		PacL1 of Mycobacterium tuberculosis

8.A.201.1.2	DUF1490 family protein of 133 aas and 1 N-terminal TMS.		DUF1490 protein of Quadrisphaera setariae

8.A.201.1.3	DUF1490 family protein of 100 aas and 1 N-terminal TMS.		DUF1490 protein of Saccharopolyspora elongata

8.A.201.1.4	DUF1490 family protein of 102 aas and 1 N-terminal TM		DUF1490 protein of Mycobacterium shottsii

8.A.201.1.5	DUF1490 family protein of 110 aas and 1 N-terminal TM		*DUF1490 protein of Chloroflexi* bacterium**

Examples:
TC#	Name	Organismal Type	Example
8.A.201.2.1	DUF6110 family protein of 116 aas and 1 N-terminal TMS		DUF6110 protein of Anaerococcus mediterraneensis

8.A.201.2.2	DUF6110 family protein of 107 aas and 1 N-terminal TMS.		DUF6110 family protein of Peptoniphilus grossensis

8.A.201.2.3	DUF6110 family protein of 94 aas and 1 N-terminal TMS.		DUF6110 protein of Urinicoccus massiliensis

8.A.201.2.4	DUF6110 family protein of 94 aas and 1 N-terminal TMS.		DUF6110 protein of Murdochiella massiliensis

8.A.201.2.5	DUF1490 family protein of 113 aas and 1 N-terminal TMS.		DUF1490 protein of Anaerococcus vaginalis